This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The NKG2A-CD94 receptor family are a large family of Natural Killer Cell receptors that play a central role in innate immunity. They act as sentinel receptors, interacting with the non-classical Major Histocompatability Complex molecule, HLA-E in complex with an MHC-1 leader peptide (pHLA-E). Recognition of this pHLA-E at the cell surface via the NKG2A receptor is a signal that the cell is healthy. However, if the pHLA-E levels are down-regulated at the cell surface, it signals that the cell is virally-infected and this leads to cell lysis. We have crystallized the NKG2A-CD94-pHLAE complex and aim to determine the high resolution structure of this complex. The proposed studies will have a profound insight into innate immunity.